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UniProtKB - Q9Y2H2 (SAC2_HUMAN)

Protein

Phosphatidylinositide phosphatase SAC2

Gene

INPP5F

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Inositol 4-phosphatase which mainly acts on phosphatidylinositol 4-phosphate. May be functionally linked to OCRL, which converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol, for a sequential dephosphorylation of phosphatidylinositol 4,5-bisphosphate at the 5 and 4 position of inositol, thus playing an important role in the endocytic recycling (PubMed:25869669). Regulator of TF:TFRC and integrins recycling pathway, is also involved in cell migration mechanisms (PubMed:25869669). Modulates AKT/GSK3B pathway by decreasing AKT and GSK3B phosphorylation (PubMed:17322895). Negatively regulates STAT3 signaling pathway through inhibition of STAT3 phosphorylation and translocation to the nucleus (PubMed:25476455). Functionally important modulator of cardiac myocyte size and of the cardiac response to stress (By similarity). May play a role as negative regulator of axon regeneration after central nervous system injuries (By similarity).By similarity3 Publications

Caution

INPP5F has been initially described as an inositol polyphosphate 5-phosphatase.1 Publication

Catalytic activityi

Myo-inositol phosphate + H2O = myo-inositol + phosphate.2 Publications

Kineticsi

  1. KM=14.3 µM for PtdIns(4,5)P2 (at pH 6.0)1 Publication

    GO - Molecular functioni

    View the complete GO annotation on QuickGO ...

    GO - Biological processi

    View the complete GO annotation on QuickGO ...

    Keywordsi

    Molecular functionHydrolase

    Enzyme and pathway databases

    BioCyciMetaCyc:HS12255-MONOMER
    ReactomeiR-HSA-1660516 Synthesis of PIPs at the early endosome membrane

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Phosphatidylinositide phosphatase SAC2Curated (EC:3.1.3.252 Publications)
    Alternative name(s):
    Inositol polyphosphate 5-phosphatase FImported
    Sac domain-containing inositol phosphatase 2
    Sac domain-containing phosphoinositide 4-phosphatase 22 Publications
    Short name:
    hSAC2
    Gene namesi
    Name:INPP5FImported
    Synonyms:KIAA0966, SAC2
    ORF Names:MSTP007, MSTP047
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
    Proteomesi
    • UP000005640 Componenti: Chromosome 10

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000198825.11
    HGNCiHGNC:17054 INPP5F
    MIMi609389 gene
    neXtProtiNX_Q9Y2H2

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Coated pit, Endosome, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi458C → S: Loss of inositol 4-phosphatase activity. Alters TFRC distribution and delays TF recycling. 1 Publication1

    Organism-specific databases

    DisGeNETi22876
    OpenTargetsiENSG00000198825
    PharmGKBiPA134927878

    Polymorphism and mutation databases

    BioMutaiINPP5F
    DMDMi187611527

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00003316211 – 1132Phosphatidylinositide phosphatase SAC2Add BLAST1132

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei827PhosphoserineBy similarity1
    Modified residuei830PhosphoserineBy similarity1
    Modified residuei878PhosphoserineBy similarity1
    Modified residuei881PhosphoserineBy similarity1
    Modified residuei907PhosphoserineCombined sources1
    Modified residuei910PhosphoserineBy similarity1
    Modified residuei1103PhosphoserineCombined sources1

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    EPDiQ9Y2H2
    PaxDbiQ9Y2H2
    PeptideAtlasiQ9Y2H2
    PRIDEiQ9Y2H2
    ProteomicsDBi85781
    85782 [Q9Y2H2-2]
    85783 [Q9Y2H2-3]

    PTM databases

    DEPODiQ9Y2H2
    iPTMnetiQ9Y2H2
    PhosphoSitePlusiQ9Y2H2
    SwissPalmiQ9Y2H2

    Expressioni

    Tissue specificityi

    Ubiquitous (PubMed:11274189). Highly expressed in brain (PubMed:26203138).2 Publications

    Gene expression databases

    BgeeiENSG00000198825 Expressed in 226 organ(s), highest expression level in pons
    CleanExiHS_INPP5F
    ExpressionAtlasiQ9Y2H2 baseline and differential
    GenevisibleiQ9Y2H2 HS

    Interactioni

    Subunit structurei

    Homodimer (PubMed:25869669). Interacts with OCRL and RAB5A (PubMed:25869668). Interacts with INPP5B and INPP4A (PubMed:25869668). Interacts with STAT3; the interaction is independent of STAT3 'TYR-705' phosphorylation status (PubMed:25476455).By similarity3 Publications

    GO - Molecular functioni

    View the complete GO annotation on QuickGO ...

    Protein-protein interaction databases

    BioGridi116543, 1 interactor
    ELMiQ9Y2H2
    IntActiQ9Y2H2, 1 interactor
    STRINGi9606.ENSP00000354519

    Structurei

    Secondary structure

    11132
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliQ9Y2H2
    SMRiQ9Y2H2
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini167 – 518SACPROSITE-ProRule annotationAdd BLAST352
    Domaini593 – 760hSac2PROSITE-ProRule annotationAdd BLAST168

    Phylogenomic databases

    eggNOGiKOG1890 Eukaryota
    COG5329 LUCA
    GeneTreeiENSGT00530000063393
    HOGENOMiHOG000139946
    HOVERGENiHBG095361
    InParanoidiQ9Y2H2
    KOiK21798
    OMAiAYCHQFV
    OrthoDBiEOG091G059J
    PhylomeDBiQ9Y2H2
    TreeFamiTF313543

    Family and domain databases

    InterProiView protein in InterPro
    IPR034753 hSac2
    IPR022158 Inositol_phosphatase
    IPR002013 SAC_dom
    PfamiView protein in Pfam
    PF12456 hSac2, 1 hit
    PF02383 Syja_N, 1 hit
    PROSITEiView protein in PROSITE
    PS51791 HSAC2, 1 hit
    PS50275 SAC, 1 hit

    Sequences (4+)i

    Sequence statusi: Complete.

    This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

    This entry has 4 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

    Isoform 1 (identifier: Q9Y2H2-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide
            10         20         30         40         50
    MELFQAKDHY ILQQGERALW CSRRDGGLQL RPATDLLLAW NPICLGLVEG 
            60         70         80         90        100
    VIGKIQLHSD LPWWLILIRQ KALVGKLPGD HEVCKVTKIA VLSLSEMEPQ 
           110        120        130        140        150
    DLELELCKKH HFGINKPEKI IPSPDDSKFL LKTFTHIKSN VSAPNKKKVK 
           160        170        180        190        200
    ESKEKEKLER RLLEELLKMF MDSESFYYSL TYDLTNSVQR QSTGERDGRP 
           210        220        230        240        250
    LWQKVDDRFF WNKYMIQDLT EIGTPDVDFW IIPMIQGFVQ IEELVVNYTE 
           260        270        280        290        300
    SSDDEKSSPE TPPQESTCVD DIHPRFLVAL ISRRSRHRAG MRYKRRGVDK 
           310        320        330        340        350
    NGNVANYVET EQLIHVHNHT LSFVQTRGSV PVFWSQVGYR YNPRPRLDRS 
           360        370        380        390        400
    EKETVAYFCA HFEEQLNIYK KQVIINLVDQ AGREKIIGDA YLKQVLLFNN 
           410        420        430        440        450
    SHLTYVSFDF HEHCRGMKFE NVQTLTDAIY DIILDMKWCW VDEAGVICKQ 
           460        470        480        490        500
    EGIFRVNCMD CLDRTNVVQA AIARVVMEQQ LKKLGVMPPE QPLPVKCNRI 
           510        520        530        540        550
    YQIMWANNGD SISRQYAGTA ALKGDFTRTG ERKLAGVMKD GVNSANRYYL 
           560        570        580        590        600
    NRFKDAYRQA VIDLMQGIPV TEDLYSIFTK EKEHEALHKE NQRSHQELIS 
           610        620        630        640        650
    QLLQSYMKLL LPDDEKFHGG WALIDCDPSL IDATHRDVDV LLLLSNSAYY 
           660        670        680        690        700
    VAYYDDEVDK VNQYQRLSLE NLEKIEIGPE PTLFGKPKFS CMRLHYRYKE 
           710        720        730        740        750
    ASGYFHTLRA VMRNPEEDGK DTLQCIAEML QITKQAMGSD LPIIEKKLER 
           760        770        780        790        800
    KSSKPHEDII GIRSQNQGSL AQGKNFLMSK FSSLNQKVKQ TKSNVNIGNL 
           810        820        830        840        850
    RKLGNFTKPE MKVNFLKPNL KVNLWKSDSS LETMENTGVM DKVQAESDGD 
           860        870        880        890        900
    MSSDNDSYHS DEFLTNSKSD EDRQLANSLE SVGPIDYVLP SCGIIASAPR 
           910        920        930        940        950
    LGSRSQSLSS TDSSVHAPSE ITVAHGSGLG KGQESPLKKS PSAGDVHILT 
           960        970        980        990       1000
    GFAKPMDIYC HRFVQDAQNK VTHLSETRSV SQQASQERNQ MTNQVSNETQ 
          1010       1020       1030       1040       1050
    SESTEQTPSR PSQLDVSLSA TGPQFLSVEP AHSVASQKTP TSASSMLELE 
          1060       1070       1080       1090       1100
    TGLHVTPSPS ESSSSRAVSP FAKIRSSMVQ VASITQAGLT HGINFAVSKV 
          1110       1120       1130 
    QKSPPEPEII NQVQQNELKK MFIQCQTRII QI
    Length:1,132
    Mass (Da):128,407
    Last modified:April 29, 2008 - v3
    Checksum:i853719FC0AD455CD
    GO
    Isoform 2 (identifier: Q9Y2H2-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         373-375: VII → QQK
         376-1132: Missing.

    Show »
    Length:375
    Mass (Da):43,817
    Checksum:iE9A76393F10C6CC3
    GO
    Isoform 3 (identifier: Q9Y2H2-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         206-219: DDRFFWNKYMIQDL → PLTARRAGFALGKK
         220-1132: Missing.

    Show »
    Length:219
    Mass (Da):25,174
    Checksum:i8AAA498682414245
    GO
    Isoform 4 (identifier: Q9Y2H2-4) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-19: MELFQAKDHYILQQGERAL → MCHDVIFMAWLKQQFSECT
         20-629: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:522
    Mass (Da):57,800
    Checksum:i8A15030B00C8E9A1
    GO

    Computationally mapped potential isoform sequencesi

    There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    		Gene namesLengthAnnotation
    A0A0J9YY79A0A0J9YY79_HUMAN
    Phosphatidylinositide phosphatase S...
    INPP5F
    		183Annotation score:
    A0A0J9YWP2A0A0J9YWP2_HUMAN
    Phosphatidylinositide phosphatase S...
    INPP5F
    		105Annotation score:
    A0A0J9YYL5A0A0J9YYL5_HUMAN
    Phosphatidylinositide phosphatase S...
    INPP5F
    		82Annotation score:
    A0A0J9YVW6A0A0J9YVW6_HUMAN
    Phosphatidylinositide phosphatase S...
    INPP5F
    		57Annotation score:
    A0A1B0GUS5A0A1B0GUS5_HUMAN
    Phosphatidylinositide phosphatase S...
    INPP5F
    		153Annotation score:

    Sequence cautioni

    The sequence BAA76810 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti386I → V in AAI11494 (PubMed:15489334).Curated1
    Sequence conflicti654Y → N in BAG52363 (PubMed:14702039).Curated1
    Sequence conflicti1008P → L in BAG52363 (PubMed:14702039).Curated1
    Sequence conflicti1019S → P in BAG52363 (PubMed:14702039).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_042907453I → V. Corresponds to variant dbSNP:rs3736822Ensembl.1
    Natural variantiVAR_042908997N → D2 PublicationsCorresponds to variant dbSNP:rs3188055Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0463661 – 19MELFQ…GERAL → MCHDVIFMAWLKQQFSECT in isoform 4. 1 PublicationAdd BLAST19
    Alternative sequenceiVSP_04636720 – 629Missing in isoform 4. 1 PublicationAdd BLAST610
    Alternative sequenceiVSP_033266206 – 219DDRFF…MIQDL → PLTARRAGFALGKK in isoform 3. 1 PublicationAdd BLAST14
    Alternative sequenceiVSP_033267220 – 1132Missing in isoform 3. 1 PublicationAdd BLAST913
    Alternative sequenceiVSP_033268373 – 375VII → QQK in isoform 2. 1 Publication3
    Alternative sequenceiVSP_033269376 – 1132Missing in isoform 2. 1 PublicationAdd BLAST757

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    		AB023183 mRNA Translation: BAA76810.2 Different initiation.
    AK091448 mRNA Translation: BAG52363.1
    AC027672 Genomic DNA No translation available.
    AL133461 Genomic DNA No translation available.
    AL158014 Genomic DNA No translation available.
    CH471066 Genomic DNA Translation: EAW49379.1
    CH471066 Genomic DNA Translation: EAW49380.1
    CH471066 Genomic DNA Translation: EAW49381.1
    BC052367 mRNA Translation: AAH52367.1
    BC067820 mRNA Translation: AAH67820.1
    BC082755 mRNA Translation: AAH82755.1
    BC111493 mRNA Translation: AAI11494.1
    AL137528 mRNA Translation: CAB70792.1
    AF113227 mRNA Translation: AAG39298.1
    AF109361 mRNA Translation: AAQ13509.1
    CCDSiCCDS58098.1 [Q9Y2H2-4]
    CCDS7616.1 [Q9Y2H2-1]
    CCDS81513.1 [Q9Y2H2-3]
    PIRiT46372
    RefSeqiNP_001230123.1, NM_001243194.1 [Q9Y2H2-4]
    NP_001230124.1, NM_001243195.1 [Q9Y2H2-3]
    NP_055752.1, NM_014937.3 [Q9Y2H2-1]
    UniGeneiHs.369755

    Genome annotation databases

    EnsembliENST00000361976; ENSP00000354519; ENSG00000198825 [Q9Y2H2-1]
    ENST00000369080; ENSP00000358076; ENSG00000198825 [Q9Y2H2-4]
    ENST00000369081; ENSP00000489864; ENSG00000198825 [Q9Y2H2-3]
    GeneIDi22876
    KEGGihsa:22876
    UCSCiuc001leo.4 human [Q9Y2H2-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    		AB023183 mRNA Translation: BAA76810.2 Different initiation.
    AK091448 mRNA Translation: BAG52363.1
    AC027672 Genomic DNA No translation available.
    AL133461 Genomic DNA No translation available.
    AL158014 Genomic DNA No translation available.
    CH471066 Genomic DNA Translation: EAW49379.1
    CH471066 Genomic DNA Translation: EAW49380.1
    CH471066 Genomic DNA Translation: EAW49381.1
    BC052367 mRNA Translation: AAH52367.1
    BC067820 mRNA Translation: AAH67820.1
    BC082755 mRNA Translation: AAH82755.1
    BC111493 mRNA Translation: AAI11494.1
    AL137528 mRNA Translation: CAB70792.1
    AF113227 mRNA Translation: AAG39298.1
    AF109361 mRNA Translation: AAQ13509.1
    CCDSiCCDS58098.1 [Q9Y2H2-4]
    CCDS7616.1 [Q9Y2H2-1]
    CCDS81513.1 [Q9Y2H2-3]
    PIRiT46372
    RefSeqiNP_001230123.1, NM_001243194.1 [Q9Y2H2-4]
    NP_001230124.1, NM_001243195.1 [Q9Y2H2-3]
    NP_055752.1, NM_014937.3 [Q9Y2H2-1]
    UniGeneiHs.369755

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    		PDB entryMethodResolution (Å)ChainPositionsPDBsum
    4XUUX-ray2.62A/B/C/D593-760[»]
    ProteinModelPortaliQ9Y2H2
    SMRiQ9Y2H2
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi116543, 1 interactor
    ELMiQ9Y2H2
    IntActiQ9Y2H2, 1 interactor
    STRINGi9606.ENSP00000354519

    PTM databases

    DEPODiQ9Y2H2
    iPTMnetiQ9Y2H2
    PhosphoSitePlusiQ9Y2H2
    SwissPalmiQ9Y2H2

    Polymorphism and mutation databases

    BioMutaiINPP5F
    DMDMi187611527

    Proteomic databases

    EPDiQ9Y2H2
    PaxDbiQ9Y2H2
    PeptideAtlasiQ9Y2H2
    PRIDEiQ9Y2H2
    ProteomicsDBi85781
    85782 [Q9Y2H2-2]
    85783 [Q9Y2H2-3]

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000361976; ENSP00000354519; ENSG00000198825 [Q9Y2H2-1]
    ENST00000369080; ENSP00000358076; ENSG00000198825 [Q9Y2H2-4]
    ENST00000369081; ENSP00000489864; ENSG00000198825 [Q9Y2H2-3]
    GeneIDi22876
    KEGGihsa:22876
    UCSCiuc001leo.4 human [Q9Y2H2-1]

    Organism-specific databases

    CTDi22876
    DisGeNETi22876
    EuPathDBiHostDB:ENSG00000198825.11
    GeneCardsiINPP5F
    HGNCiHGNC:17054 INPP5F
    MIMi609389 gene
    neXtProtiNX_Q9Y2H2
    OpenTargetsiENSG00000198825
    PharmGKBiPA134927878
    HUGEiSearch...
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1890 Eukaryota
    COG5329 LUCA
    GeneTreeiENSGT00530000063393
    HOGENOMiHOG000139946
    HOVERGENiHBG095361
    InParanoidiQ9Y2H2
    KOiK21798
    OMAiAYCHQFV
    OrthoDBiEOG091G059J
    PhylomeDBiQ9Y2H2
    TreeFamiTF313543

    Enzyme and pathway databases

    BioCyciMetaCyc:HS12255-MONOMER
    ReactomeiR-HSA-1660516 Synthesis of PIPs at the early endosome membrane

    Miscellaneous databases

    ChiTaRSiINPP5F human
    GenomeRNAii22876
    PROiPR:Q9Y2H2
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000198825 Expressed in 226 organ(s), highest expression level in pons
    CleanExiHS_INPP5F
    ExpressionAtlasiQ9Y2H2 baseline and differential
    GenevisibleiQ9Y2H2 HS

    Family and domain databases

    InterProiView protein in InterPro
    IPR034753 hSac2
    IPR022158 Inositol_phosphatase
    IPR002013 SAC_dom
    PfamiView protein in Pfam
    PF12456 hSac2, 1 hit
    PF02383 Syja_N, 1 hit
    PROSITEiView protein in PROSITE
    PS51791 HSAC2, 1 hit
    PS50275 SAC, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiSAC2_HUMAN
    AccessioniPrimary (citable) accession number: Q9Y2H2
    Secondary accession number(s): B3KRF1
    , D3DRD1, Q2T9J4, Q5W135, Q5W136, Q6NVY2, Q86U97, Q9H3D9, Q9NT51
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 29, 2008
    Last sequence update: April 29, 2008
    Last modified: November 7, 2018
    This is version 127 of the entry and version 3 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    2. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    3. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    4. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    5. Human chromosome 10
      Human chromosome 10: entries, gene names and cross-references to MIM
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